Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Continued Examination under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission of RCE on January 7, 2026 and amendment after final filed on December 8, 2025 has been entered. Claim 1 was amended and claims 2-7, 11, 13, 15, 17-19, 24, 27 were canceled. Claims 1, 8-10, 12, 14, 16, 20-23, 25-26 and 28 are pending in the instant application.
The restriction requirement was deemed proper and made FINAL previously. Claims 8-10, 12, 14, 16, 20-23, 25-26 and 28 remain withdrawn from consideration as being drawn to a non-elected invention/species. Claim 1 is examined on the merits of this office action.
Withdrawn Rejections
The rejection of claims 1, 15, 18 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, scope of enablement is withdrawn in view of amendment of the claims filed December 8, 2025.
The rejection of Claim(s) 1, 15 and 18 under 35 U.S.C. 103 as being unpatentable over Hawiger (US2004235746 cited in Applicant’s IDS) in view of Hawiger* (US20140309159 A1, cited previously) is withdrawn in view of amendment of the claims filed December 8, 2025.
Maintained/Revised Rejections
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1 remains provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 8, 11-19, 21, 23 of copending Application No. 18/479600 (reference application) in view of Hawiger,Allergy and Asthma Network and Homey (see below reference citations). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims: A method of treating/inhibiting/reducing atopic dermatitis being mediated by TNFa, IL-1, IL-6, IL-10, Il-17 or MCP-1 the method comprising administering to the subject a therapeutically effective amount of a composition comprising a Nuclear Transport Modifier (NTM); wherein the NTM comprises the sequence set forth in SEQ ID NO: 2, SEQ ID SEQ ID NO: 5; SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and/or SEQ ID NO: 16” (see claim 1).
Co-pending Application No. 18479600 claims a method of treating microbial inflammation in a subject comprising administering an NTM (claim 1) wherein the NTM comprises SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3; SEQ ID NO: 4; SEQ ID NO: 5; SEQ ID NO: 6 or SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 16 (see claim 5). Microbial infection/inflammation is mediated by TNF-a and IL-6. The sequences are identical to the instant claimed sequences. Co-pending Application No. 18479600 further claims wherein the infection is in the skin (see claim 6). The co-pending Application claims the identical peptides, targeting inflammatory conditions (microbial infections) mediated by cytokines using the same mechanism of action (nuclear transport inhibition) and administered to same organ (skin). Co-pending Application No. 18479600 is silent to treating atopic dermatitis.
The difference in the treated condition represents an obvious variation of the copending claimed methods. The prior art, including Hawiger (see below teachings), teaches that NTM peptides function by inhibiting nuclear transport of pro-inflammatory transcription factors (e.g., NF-κB) and suppressing cytokine-mediated inflammatory responses in inflammatory skin diseases including eczema and contact dermatitis. The additional references (Allergy and Asthma Network) and Homey teach that atopic dermatitis is a cytokine-mediated inflammatory skin disease and is the most common form of eczema. In view of the shared peptide class, shared mechanism of action, and overlapping inflammatory cytokine pathways, it would have been an obvious variant to apply the same NTM peptides recited in the copending claims to the treatment of atopic dermatitis. Accordingly, the instant claims are not patentably distinct from the copending claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Applicant’s Arguments
Applicants note that US Application NO. 18/479,600 is a later filed application. Accordingly, as noted in MPEP 1490 VI(D)(2)(a)
Applicants respectfully assert that because U.S. Application No. 18/479,600 is the later filed application, the appropriate application for submission of a terminal disclaimer, making arguments regarding the obviousness of the pending claims as it relates to alleged double patenting, or amending distinguishing claims is in U.S. Application No. 18/479,600. Accordingly, in view of the present amendments and because the cited art is the later filed application, Applicants assert that the present rejection is not properly applied to the present case and respectfully request its withdrawal.
Applicants arguments have been fully considered but not found persuasive. Applicant argues that U.S. Application No. 18/479,600 is a later-filed application and therefore the present nonstatutory double patenting rejection is improper and should instead be addressed in that application. This argument is not persuasive. A nonstatutory obviousness-type double patenting rejection is based on a comparison of the claims of the instant application and the claims of a commonly owned copending or patented application to determine whether the claimed subject matter is patentably distinct. The rejection is not dependent on which application was filed first. See MPEP §804 and §1490(VI)(D)(2)(a). Such a rejection may properly be applied in either application where the claims are not patentably distinct and common ownership exists or is expected. Once the instant application is otherwise in condition for allowance, the issue of relative filing dates are then taken into account (the rejection is dropped if the instant application has an earlier filing date). Furthermore, regarding Applicants arguments that amendment of the instant claims overcome the double patenting rejection (due to requirement of treating atopic dermatitis), the Examiner respectfully disagrees.
The Examiner acknowledges that Co-pending Application No. 18479600 is silent to treating atopic dermatitis.
However, the difference in the treated condition represents an obvious variation of the copending claimed methods. The prior art, including Hawiger (see below teachings), teaches that NTM peptides function by inhibiting nuclear transport of pro-inflammatory transcription factors (e.g., NF-κB) and suppressing cytokine-mediated inflammatory responses in inflammatory skin diseases including eczema and contact dermatitis. The additional references (Allergy and Asthma Network and Homey) teach that atopic dermatitis is a cytokine-mediated inflammatory skin disease and is the most common form of eczema. In view of the shared peptide class, shared mechanism of action, and overlapping inflammatory cytokine pathways, it would have been an obvious variant to apply the same NTM peptides recited in the copending claims to the treatment of atopic dermatitis. Accordingly, the instant claims are not patentably distinct from the copending claims.
Claim 1 remains provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of co-pending Application No. 18/939615 (reference application) in view of Hawiger (US2004235746 cited in Applicant’s IDS) Allergy and Asthma Network and Homey (see below reference citations). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims: A method of treating/inhibiting/reducing atopic dermatitis being mediated by TNFa, IL-1, IL-6, IL-10, Il-17 or MCP-1 the method comprising administering to the subject a therapeutically effective amount of a composition comprising a Nuclear Transport Modifier (NTM); wherein the NTM comprises the sequence set forth in SEQ ID NO: 2, SEQ ID SEQ ID NO: 5; SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and/or SEQ ID NO: 16” (see claim 1).
Co-pending Application No. 18/939615 “A method of treating/inhibiting/reducing an inflammatory skin disease or inflammatory skin disorder caused by microbial, allergic, autoimmune, constitutive, metabolic, neoplastic and/or physical insults in a subject comprising…a therapeutically effective amount of a composition comprising a Nuclear Transport Checkpoint Inhibitor (NTCI)” (claim 1). Copending Application No. 18/939615 further claims “wherein the NTCI comprises the sequence set forth in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3; SEQ ID NO: 4; SEQ ID NO: 5; SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19; SEQ ID NO: 20; SEQ ID NO: 21; SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29; SEQ ID NO: 30; SEQ ID NO: 31; SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39; SEQ ID NO: 40; and/or SEQ ID NO: 41” (which are identical to the instant claims, see claim 2). Copending Application No. 18/939615 claims treating skin infections (claim 3); wherein the inflammatory skin disorder is caused by physical injury selected from the group consisting of abrasion, puncture, laceration, contusion, blunt force trauma, ischemia, surgery, bedsores, electric burn, sunburn, chemical burn, high temperature burn, low temperature burn, radiation injury, and skin aging (Claim 9); Skin Atrophy, Skin Aging, Xanthelasma, metabolic syndrome, diabetes mellitus, obesity, Gaucher’s disease, Phenylketonuria (PKU), Maple syrup urine disease (MSUD), fatty liver, hypercholesterolemia, hypertriglyceridemia, hyperthyroidism, hypothyroidism, dyslipidemia, hypolipidemia, seborrheic dermatitis, and galactosemia (claim 8). Co-pending Application No. 18/939615 doesn’t specifically claim wherein the autoimmune condition is atopic dermatitis or eczema .
Hawiger teaches that “Such NF-κB NLS-based peptides (i.e. SN50 or cSN50) can be used to treat, prevent, or reduce the effects of inflammatory diseases and conditions of the skin involving autoimmune or allergic responses, for example, but not limited to, psoriasis, eczema, contact dermatitis” (See paragraph 0157).
The additional references (Allergy and Asthma Network) and Homey teaches that atopic dermatitis is a cytokine-mediated inflammatory skin disease and is the most common form of eczema (see below rejection).
The co-pending Application claims the identical peptides, targeting inflammatory conditions (autoimmune and autoinflammatory) and physical injury mediated by cytokines using the same mechanism of action (nuclear transport inhibition) and administered to same organ (skin). A person of ordinary skill the art would have had a reasonable expectation of success in applying the NTMs disclosed in the co-pending application to treat skin inflammation mediated by cytokines regardless of whether the underlying cause is microbial, autoimmune or autoinflammatory. Furthermore, it would have been obvious to treat atopic dermatitis and eczema with the NTMs of the co-pending application. One of ordinary skill in the art would have been motivated to do so given Hawiger teaches the NTM peptides can be used to treat psoriasis, eczema, contact dermatitis and these disorders are encompassed by the genus of autoimmune/autoinflammatory disease as claimed by Co-pending Application No. 18/939615.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Applicant’s Arguments
Applicants respectfully request that the rejection be reconsidered in light of this amendment.
Moreover, Applicants note that US Application NO. 18/939,615 is a later filed application. Accordingly, as noted in MPEP 1490 VI(D)(2)(a) If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent. Applicants respectfully assert that because U.S. Application No. 18/939,615 is the later filed application, the appropriate application for submission of a terminal disclaimer, making arguments regarding the obviousness of the pending claims as it relates to alleged double patenting, or amending distinguishing claims is in U.S. Application No. 18/939,615. Accordingly, in view of the present amendments and because the cited art is the later filed application, Applicants assert that the present rejection is not properly applied to the present case and respectfully request its withdrawal.
Applicants arguments have been fully considered but not found persuasive. Applicant argues that U.S. Application No. 18/939615 is a later-filed application and therefore the present nonstatutory double patenting rejection is improper and should instead be addressed in that application. This argument is not persuasive. A nonstatutory obviousness-type double patenting rejection is based on a comparison of the claims of the instant application and the claims of a commonly owned copending or patented application to determine whether the claimed subject matter is patentably distinct. The rejection is not dependent on which application was filed first. See MPEP §804 and §1490(VI)(D)(2)(a). Such a rejection may properly be applied in either application where the claims are not patentably distinct and common ownership exists or is expected. Once the instant application is otherwise in condition for allowance, the issue of relative filing dates are then taken into account (the rejection is dropped if the instant application has an earlier filing date). Furthermore, regarding Applicants arguments that amendment of the instant claims overcome the double patenting rejection (due to requirement of treating atopic dermatitis), the Examiner respectfully disagrees.
The Examiner acknowledges that Co-pending Application No. 18/939615 doesn’t specifically claim wherein the autoimmune condition is atopic dermatitis or eczema .
Hawiger teaches that “Such NF-κB NLS-based peptides (i.e. SN50 or cSN50) can be used to treat, prevent, or reduce the effects of inflammatory diseases and conditions of the skin involving autoimmune or allergic responses, for example, but not limited to, psoriasis, eczema, contact dermatitis” (See paragraph 0157).
The additional references (Allergy and Asthma Network) and Homey teaches that atopic dermatitis is a cytokine-mediated inflammatory skin disease and is the most common form of eczema (see below rejection).
The co-pending Application claims the identical peptides, targeting inflammatory conditions (autoimmune and autoinflammatory) and physical injury mediated by cytokines using the same mechanism of action (nuclear transport inhibition) and administered to same organ (skin). A person of ordinary skill the art would have had a reasonable expectation of success in applying the NTMs disclosed in the co-pending application to treat skin inflammation mediated by cytokines regardless of whether the underlying cause is microbial, autoimmune or autoinflammatory. Furthermore, it would have been obvious to treat atopic dermatitis and eczema with the NTMs of the co-pending application. One of ordinary skill in the art would have been motivated to do so given Hawiger teaches the NTM peptides can be used to treat psoriasis, eczema, contact dermatitis and these disorders are encompassed by the genus of autoimmune/autoinflammatory disease as claimed by Co-pending Application No. 18/939615.
New Rejections
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1 is rejected under 35 U.S.C. 103 as being unpatentable over Hawiger (US2004235746 cited in Applicant’s IDS) in view of Hawiger* (US20140309159 A1, cited previously) and Allergy and Asthma Network (published on line 2018) and Homey (J ALLERGY CLIN IMMUNOL. VOLUME 118, NUMBER 1.
Hawiger discloses a method of using cSN50 (which comprises instant SEQ ID NO:4 (no longer in the claim but structurally similar to other SEQ ID Nos in the claim, see SEQ ID NO:12) for treatment of an inflammatory response in a subject and an inflammatory skin condition (see claim 17) which is caused by the toxin or an allergen (see paragraph 0065 and also Example VII). Hawiger teaches that “Such NF-κB NLS-based peptides (i.e. SN50 or cSN50) can be used to treat, prevent, or reduce the effects of inflammatory diseases and conditions of the skin involving autoimmune or allergic responses, for example, but not limited to, psoriasis, eczema, contact dermatitis” (See paragraph 0157). Hawiger further teaches that the inflammatory conditions targeted by the NTMs involve upregulation of proinflammatory cytokines including TNFa, IL-1 and IL-16 (see paragraphs 0111, 0051) and that treatment suppresses expression of these cytokines by interfering with nuclear translocation of transcription factors such as NFKB and STAT1 (see claim 21, paragraph 0069). Regarding claim 1, Hawiger teaches treatment of inflammatory skin conditions including psoriasis, eczema and contact dermatitis (0067 and 0157).
Hawiger is silent as to certain specific NTM peptide sequence variants as recited in the instant claims and specifically atopic dermatitis.
However Hawiger* teaches a composition for inflammatory disease or disorder in a subject comprising a pharmaceutically acceptable carrier and at least one importin beta-selective nuclear transport modifier (NTM) (see claim 1) and treating said disease/disorder. Hawiger* teaches wherein the NTM has SEQ ID NO:2 which is identical to instant SEQ ID NO:16 and also SEQ ID NO:5 (cSN50.1,SEQ ID NO:5) which is identical to instant SEQ ID NO:2. Hawiger* teaches modification of cSN50 to improve solubility (see paragraph 0051). Hawiger* teaches that the disclosed NTM peptides are useful for treating inflammatory diseases and disorders mediated by cytokine activity and nuclear transport of transcription factors, including inflammatory skin diseases and autoimmune or autoinflammatory conditions (see paragraphs 0007, 0067-0069). Hawiger* teaches the NTM peptide (instant SEQ ID NO:2) suppressed mediators of inflammation (TNF-alpha, IL-6) which are dependent on importin alpha mediated nuclear transport of proinflammatory SRTFs (see figure 10).
Allergy and Asthma Network teaches “Atopic dermatitis is a chronic inflammatory skin condition. It is the most common type of eczema” (see “Atopic Dermatitis”).
Homey teaches Atopic dermatitis (AD) is a common pruritic and chronically relapsing inflammatory skin disease with a steadily increasing prevalence (see abstract). Homey teaches that atopic dermatitis is a cytokine-mediated inflammatory skin disease involving TNF and interleukin signaling pathways (see Figure 1).
It would have been obvious before the effective filing date of the claimed invention to use the specific NTM peptide sequence variants taught by Hawiger* in the inflammatory skin disease treatment (eczema, dermatitis) of Hawiger. One of ordinary skill in the art would have been motivated to do so since both references teach the same class of NF-kB nuclear transport inhibitory peptides, the same mechanism of action (inhibition of nuclear import of proinflammatory transcription factors), and the same target disease space (inflammatory and autoimmune skin disorders including eczema (a type of atopic dermatitis) and contact dermatitis. Given the shared mechanism of action, overlapping peptides and overlapping therapeutic targets, a person of ordinary skill in the art would have had a reasonable expectation of success in sing the specific NTM peptide variants disclosed in Hawiger* including SEQ IDNO:2 and SEQ ID NO:5 variants, in the treatment methods of Hawiger. One of ordinary skill in the art would have been further motivated to use the Variants of Hawiger* given Hawiger* teaches the modification improved solubility which would be beneficial for therapeutic use.
Furthermore, the claimed peptides are different from the Hawiger by at most a limited amino acid substitution associated with improved solubility (see paragraph 0051). Hawiger* expressly teaches closely related sequence variants and substitutions to improve solubility and usability of NTM peptides. Optimization of peptide solubility and related formulation properties to improve therapeutic use through amino acid substitution represents routine and predictable optimization of a result effective variable in peptide arts. Such modification would have been obvious choice for one of ordinary skill in the art Under KSR (see MPEP 2141 III), where the prior art teaches the use of a known compound or class of compounds to treat related conditions involving the same biological mechanism, applying known sequence variants of that compound in an analogous therapeutic setting is an obvious variation.
Regarding treatment of atopic dermatitis, It would have been obvious before the effective filing date of the claimed invention to use the specific NTM peptide sequence variants taught by Hawiger in view of Hawiger* for treatment of atopic dermatitis. Hawiger teaches NF-κB nuclear transport inhibitory peptides useful for treating inflammatory and autoimmune skin disorders including eczema and contact dermatitis, while Hawiger* further teaches specific NTM peptide species and sequence variants and confirms their anti-inflammatory activity and suitability for therapeutic use. Allergy and Asthma Network teaches that atopic dermatitis is a chronic inflammatory skin condition and the most common form of eczema and Homey teaches that it is mediated by in part by inflammatory cytokines. Because the references teach the same class of peptides, the same mechanism of action (inhibition of nuclear import of pro-inflammatory transcription factors), and overlapping inflammatory skin disease targets, one of ordinary skill in the art would have been motivated to apply the Hawiger in view of Hawiger* peptides to atopic dermatitis with a reasonable expectation of success.
Regarding claim 1, the claim further recites that atopic dermatitis is mediated by TNF-α, IL-1, IL-6, IL-10, IL-17, or MCP-1. Hawiger teaches that the disclosed nuclear transport modifier peptides inhibit nuclear import of NF-κB and related transcription factors and thereby suppress pro-inflammatory cytokines including TNF-α, IL-1, and IL-6. Because the claim is written in the alternative (“or”), teaching suppression of one or more of the recited cytokines satisfies this limitation. Additionally, Homey teaches that atopic dermatitis is a cytokine-mediated inflammatory skin disease involving TNF and interleukin signaling pathways (see Figure 1). Therefore, the combined references teach and suggest treatment of atopic dermatitis mediated by the recited cytokines using the claimed peptide class.
Response to Applicant’s Arguments
Applicant argues “Furthermore, in order to establish a prima facie case of obviousness, the examiner has the initial burden of supporting the conclusion of non-obviousness. In particular, the Examiner has the initial burden of ascertaining the differences between the claims and the prior art which requires interpreting both the art and the claims as a whole. Put another way, "all words in a claim must be considered in judging the patentability of that claim against the prior art." In re Wilson, 424 F.2d 1382, 1385, 165 USPQ 494, 496 (CCPA 1970). Thus, the combination of the '746 application and the '159 application must still be able to account for all the limitations of the claims otherwise a single reference teaching a single aspect of a claim without further disclosure or knowledge in the art would be able to render a claim obvious and subsequently render all innovation moot. Applicant asserts that it is this important consideration that has not been met with respect to the present claims. In fact, none of the art cited alone, or in combination with or without the general knowledge of the art at the time the application was filed, can account for all the limitations of Claim 1, let alone Claims 15 and 18 which are dependent thereon. As currently amended, Claim 1 recites "A method of treating/inhibiting/reducing atopic dermatitis in a subject with said atopic dermatitis, said atopic dermatitis being mediated by TNF-a, IL-1, IL-6,
IL-10, IL-17, and/or MCP-1; the method comprising administering to the subject a therapeutically effective amount of a composition comprising a Nuclear Transport Modifier (NTM); wherein the NTM comprises the sequence set forth in SEQ ID NO: 2, SEQ ID NO: 5; SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9,
and/or SEQ ID NO: 16."
Applicant argues that none of the cited references, alone or in combination, teach or suggest a method of treating atopic dermatitis mediated by TNF-α, IL-1, IL-6, IL-10, IL-17, and/or MCP-1 using the specific NTM peptides recited in the claims. Applicants arguments have been fully considered but not found persuasive. The rejection is based on the combined teachings of Hawiger in view of Hawiger* and further in view of Allergy and Asthma Network and Homey. Hawiger teaches methods of treating inflammatory skin diseases including psoriasis, eczema, and contact dermatitis using NF-κB nuclear localization sequence inhibitory peptides, and teaches that such peptides suppress pro-inflammatory cytokines including TNF-α and IL-6 through inhibition of nuclear import of stress-responsive transcription factors. Hawiger* teaches specific NTM peptide species and closely related sequence variants corresponding to and structurally highly similar to the claimed SEQ ID NO peptides, including variants differing by minor amino acid substitutions associated with improved solubility and formulation properties. Allergy and Asthma Network teaches “Atopic dermatitis is a chronic inflammatory skin condition. It is the most common type of eczema” and Homey teaches of specific cytokine involvement in Atopic dermatitis. Taken together, the references teach (i) the relevant peptide class (NTM / NF-κB nuclear transport inhibitory peptides), (ii) the specific and closely related peptide species and variants recited in the claims, (iii) treatment of inflammatory skin diseases including eczema and contact dermatitis, and (iv) cytokine-mediated inflammatory mechanisms involving TNF-α and interleukins. Atopic dermatitis is a recognized form of eczema and inflammatory skin disease and would have been understood by a person of ordinary skill in the art to fall within the taught treatment targets. Applicant’s argument improperly requires that the prior art recite the identical disease label, cytokine list, and peptide sequence set in a single reference. However, §103 does not require in haec verba disclosure of every claim phrase. In the instant case, the prior art teaches treatment of a genus of inflammatory skin diseases using peptides that inhibit NF-κB–mediated cytokine signaling, and further teaches the claimed peptide species and closely related variants, applying those peptides to treat atopic dermatitis represents a predictable use of known compounds for a closely related disease mediated by overlapping cytokine pathways. Further, the claimed peptide sequences differ from the peptides expressly taught in Hawiger* by minor amino acid substitutions associated with solubility or optimization effects, which constitutes routine sequence optimization and a predictable variation within the skill of the art. Accordingly, the examiner maintains that the combination of Hawiger in view of Hawiger* and Allergy and Asthma Network and Homey teaches or renders obvious all limitations of the pending claims.
New Rejection
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 1 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Scope of the claims
The claims are drawn to “A method of treating/inhibiting/reducing atopic dermatitis the method comprising administering to the subject a therapeutically effective amount of a composition comprising a Nuclear Transport Modifier (NTM); wherein the NTM comprises the sequence set forth in SEQ ID NO: 2, SEQ ID NO: 5; SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and/or SEQ ID NO: 16.”
Regarding NTM, Applicant’s specification states “By the phrase “nuclear transport modifier” and “NTM” is meant a peptide that is capable of modulating entry of transcription factors into the nucleus. An example of a nuclear transport modifier is a 26-29 amino acid peptide derived from human nuclear factor kappa B1 nuclear localization sequence and from human Fibroblast Growth Factor 4 signal sequence hydrophobic region. This phrase is used interchangeably with the phrase “nuclear import inhibitor.”
In an NTM as described herein, any of the amino acid residues in the NTM sequence can be mutated and/or modified (i.e., to form mimetics) so long as the modifications do not affect the translocation-mediating function of the peptide. Thus, the word “peptide” includes mimetics and the word “amino acid” includes modified amino acids, unusual amino acids, D-form amino acids, etc” (See paragraphs 0032-0033). SEQ ID Nos 2, 7, 9 and 16 are fully defined amino acid sequences. However, SEQ ID Nos:5 and 8 comprise many undefined variables. For example, SEQ ID NO;8 is a 29mer wherein 13 amino acids are undefined (X variables) and thus can be any amino acids. This leaves a peptide with as lows as 56% sequence identity to the defined peptide (cSN50/50.1).
The possibilities are enormous given the number of different peptides encompassed by variants with as much as 13 amino acids different from the defined peptide. Furthermore, Applicants provide no guidance as to which structure would be “sufficient” to have the claimed function (treat atopic dermatitis) of nuclear transport modifier.
Therefore, to meet the written description requirement of 35 U.S.C. § 112, first paragraph, the specification must disclose a representative number of species that meet both the structural and functional limitations of the genus or the specification and/or the prior art must identify the structural elements that correlate to the claimed function in a manner that demonstrates to one of ordinary skill in the art that Applicant was in possession of the claimed genus at the time the application was filed (variants encompassed by instant SEQ IDNOs:5 and 8 that is capable of treating atopic dermatitis. In the instant case, the specification must establish which of the vast number of peptide sequences/structures that satisfy the structural limitations of the claim are also capable of having the claimed therapeutic properties.
Actual Reduction to Practice
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, Applicants reduce to practice the following: Example NTM ((cSN50.1, a cyclized version of SN50) treatment in combination with PMA (Phorbol Myristoyl Acetate) on the shaved backs on mice (see Examples 1-2, PMA induced inflammation). The specification does not show treatment of any other skin disease or disorder including skin cancer and do not provide a nexus for treating PMA induced inflammation of the skin with all of the disorders encompassed by the claims or more than one NTM. As discussed above the claim scope is potentially enormous; in comparison, the scope of the description which only has cSN50.1 reduced to practice, is extremely narrow. One of ordinary skill in the art would not consider the Examples in the instant specification to be representative of the full scope of the claimed genus.
Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination thereof.
The specification identifies several species of N50 NTM (see Tables 2-3). Although one of ordinary skill in the art could determine if a given amino acid sequence meets the structural requirements of the genus, it would not be possible to determine from the sequence alone if peptide able to treat atopic dermatitis as found in instant claim 1 or have the required modifying properties. Furthermore, the possibilities are vast given that several of the SEQ ID Nos listed in instant claim 1 allow for many different substitutions without a specific structure function correlation.
Physical and/or chemical properties:
The data do not suggest the physical basis for the claimed activity and therefore do not describe which substitutions, deletions or additions could be made while preserving function. Understanding the physical basis for the claimed activity is critical to determining which of the sequences that meet the structural requirements of the genus also meet the functional requirements of the genus (the desired therapeutic properties). In the instant case, Applicants are claiming a function (nuclear transport modifier and therapeutic for atopic dermatitis) without ample structure provided for two of the SEQ ID NOs.
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The specification does not describe a general correlation between structure and function for the claimed genus. The role of the individual amino acids of SN50 in treating atopic dermatitis and the claimed functional effects is not described. As a result, it is impossible to predict, based on the specification, how changing any position (or the structure) will affect the ability of the compound to modulate nuclear transport and treat atopic dermatitis along with the claimed inflammatory functional effects.
Method of Making
Solid state peptide synthesis and cloning, recombinant expression and purification of proteins is well-known in the art are listed as the methods for making the peptides of the instant claims. Where the specification fails to provide description is in the structure of the NTM make (in particular with respect to SEQ IDNOs:5 and 8). For all of the reasons presented above, one of ordinary skill in the art would not know which of the peptide variants encompassed by the claims that meet the structural requirements of the claims would also be able to be treat atopic dermatitis and have the specific anti-inflammatory effects as found in instant claim 1.
The Applicant’s specification lacks guidance as to which NTMs encompassed by the claim would retain the desired therapeutic activity. Thus, it is not possible for one of ordinary skill in the art to distinguish based on sequence alone/structure alone which sequences will retain the ability to treat atopic dermatitis and modulate specific inflammatory markers found in instant claim 1.
Conclusion
In conclusion, only the specifically defined NTMs reduced to practice satisfies the written description requirements of 35 U.S.C. 112, first paragraph.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of US Patent No. 11771739 in view of Hawiger,Allergy and Asthma Network and Homey (see below reference citations). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims: A method of treating/inhibiting/reducing atopic dermatitis being mediated by TNFa, IL-1, IL-6, IL-10, Il-17 or MCP-1 the method comprising administering to the subject a therapeutically effective amount of a composition comprising a Nuclear Transport Modifier (NTM); wherein the NTM comprises the sequence set forth in SEQ ID NO: 2, SEQ ID SEQ ID NO: 5; SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and/or SEQ ID NO: 16” (see claim 1).
US Patent No. ‘739 claims a method of treating microbial inflammation in a subject comprising administering an NTM (claim 1) wherein the NTM comprises SEQ ID NO: 2, ID NO: 6 or SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, or SEQ ID NO: 16 (see claim 5). Microbial infection/inflammation is mediated by TNF-a and IL-6. The sequences are identical to the instant claimed sequences. US Patent No. ‘739 further claims wherein the infection is in the skin (see claim 5). US Patent No. ‘739 claims the identical peptides, targeting inflammatory conditions (microbial infections in the skin) mediated by cytokines using the same mechanism of action (nuclear transport inhibition) and administered to same organ (skin). US Patent NO. ‘739 is silent to treating atopic dermatitis.
The difference in the treated condition represents an obvious variation of the copending claimed methods. The prior art, including Hawiger (see below teachings), teaches that NTM peptides function by inhibiting nuclear transport of pro-inflammatory transcription factors (e.g., NF-κB) and suppressing cytokine-mediated inflammatory responses in inflammatory skin diseases including eczema and contact dermatitis. The additional references (Allergy and Asthma Network) and Homey teach that atopic dermatitis is a cytokine-mediated inflammatory skin disease and is the most common form of eczema. In view of the shared peptide class, shared mechanism of action, and overlapping inflammatory cytokine pathways, it would have been an obvious variant to apply the same NTM peptides recited in the US Patent No. ‘739 to the treatment of atopic dermatitis. Accordingly, the instant claims are not patentably distinct from the copending claims.
Conclusion
NO claims are allowed.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654